The application proposes continuation of a resource project that has been continuously managed by the principal investigators for over 16 years. The project purpose has 2 parts. The first is to serve as a central research resource for production and distribution, to other independent research investigators, of 4 canine mutant models of the hereditary retinal degenerations affecting humans. The need for these canine mutants in research is addressed, as is the importance of maintaining them in a centralized breeding and distribution facility. The second objective is to continue collaborative studies already established to clone the genes for these diseases, investigate the cellular and molecular biology of these diseases, and develop methods for therapeutic intervention. Each such collaborative study is peer reviewed, separately, as part of the collaborative investigators' research protocols. Four strains of dogs, each transmitting a different gene for well characterized hereditary retinal degenerations (rod-cone dysplasia type 1 rcd1, progressive rod-cone degeneration prcd, early retinal degeneration erd, cone degeneration cd), together with appropriate nonaffected control dogs, will be bred and maintained. The progeny of these dogs will be distributed to research investigators, either directly or by collection, processing and distribution of requested tissues. Utilization of these mutants will be promoted by solicitation of requests from investigators. Assistance will be offered to investigators in development and implementation of specific protocols for optimal utilization of these mutants. Specific collaborative research includes programs to: identify, clone, and characterize the gene mutations for cd, erd and prcd; determine and compare the role of programmed cell death genes in cd,erd, prcd, and rcd1; define the cause of abnormalities in docosahexanoic acid transport & metabolism in prcd and identify candidate genes responsible for these deficiencies; further develop therapies for hereditary retinal degenerations including vector mediated gene transfer into canine photoreceptors; photoreceptor and retinal pigment epithelial cell transplantation into canine retina; and application of a visual-prosthetic silicon retinal implant.